Tumor associated microglia/macrophages utilize GPNMB to promote tumor growth and alter immune cell infiltration in glioma.
Fatih YalcinHannah HanekeIbrahim E EfeLeonard D KuhrtEdyta MottaBernadette NicklCharlotte FlühMichael SynowitzOmar DzayeMichael BaderHelmut KettenmannPublished in: Acta neuropathologica communications (2024)
Tumor-associated microglia and blood-derived macrophages (TAMs) play a central role in modulating the immune suppressive microenvironment in glioma. Here, we show that GPNMB is predominantly expressed by TAMs in human glioblastoma multiforme and the murine RCAS-PDGFb high grade glioma model. Loss of GPNMB in the in vivo tumor microenvironment results in significantly smaller tumor volumes and generates a pro-inflammatory innate and adaptive immune cell microenvironment. The impact of host-derived GPNMB on tumor growth was confirmed in two distinct murine glioma cell lines in organotypic brain slices from GPNMB-KO and control mice. Using published data bases of human glioma, the elevated levels in TAMs could be confirmed and the GPNMB expression correlated with a poorer survival.
Keyphrases
- endothelial cells
- high grade
- stem cells
- immune response
- inflammatory response
- induced pluripotent stem cells
- systematic review
- pluripotent stem cells
- low grade
- randomized controlled trial
- machine learning
- type diabetes
- metabolic syndrome
- multiple sclerosis
- skeletal muscle
- white matter
- electronic health record
- long non coding rna
- brain injury
- binding protein
- resting state
- high fat diet induced
- artificial intelligence
- wild type
- subarachnoid hemorrhage
- functional connectivity